A proposal is made to develop quantitative 3-dimensional magnetic resonance imaging (MRI) with microscopic resolution as an in vivo assay for the response of small animals to environmental toxins. Specifically the proposal will develop MR pulse sequences for accurate determination of spin-lattice (T1) and spin-spin (T2) relaxation times over 8-32 contiguous 1 mm thick slices with resolution of less than 100 microns. The improved accuracy and high resolution will remove the systematic errors and volume averaging that have limited the specificity of MRI in previous studies. The sequences optimized for small animal imaging will be applied to studies of three environmental toxins in the rat: carbon tetrachloride, alpha-naphthlisothiocyanate, and diethyl nitrosamine. Histogram analysis of T1/T2 images will be correlated with morphometric histologic examination to determine the sensitivity and specificity of MR in evaluating fatty change, fibrosis, necrosis, and neoplasia in the liver. The methods developed will replace the more costly and time consuming techniques of necropsy. Of particular interest is the fact that the techniques do not require sacrifice of the animal. Thus, the time course of a study can be followed in a single animal, reducing the number of animals required and permitting the study of progression and regression in the toxic response. The work promises a new approach to the study of toxicology using in vivo histology.